Transplacental Transfer of Lumefantrine, Mefloquine, and Piperaquine: A Comparison of Concentrations in Mothers, Neonates, and Cord Blood.

Abstract

Malaria in pregnancy causes adverse effects on the mother and fetus, requiring effective antimalarial treatment. Understanding the transplacental transfer of antimalarials is vital to assessing fetal safety and the risk of congenital malaria. We assessed a triad of blood samples (mother and neonatal capillary, cord) at delivery among women who were treated for uncomplicated malaria with artemether-lumefantrine (AL), artesunate-mefloquine (ASMQ), or dihydroartemisinin-piperaquine (DP) 4-8 weeks before delivery. Antimalarial drug concentrations at delivery were measured in 90 women (25 AL, 29 ASMQ, 36 DP). Drug concentrations were detectable in neonates at birth at a maximum of 27, 42, and 55 days after the first dose of lumefantrine, mefloquine, and piperaquine, respectively. The blood concentrations were highest in the mother, followed by the neonate, and lowest in cord blood. Piperaquine showed the highest neonate-to-mother (N/M) ratio (geometric mean, 0.98; 95% confidence interval, 0.67-1.44; n = 32) followed by carboxy-mefloquine (0.90; 0.75-1.08; n = 27), desbutyl-lumefantrine (0.44; 0.30-0.65; n = 16), mefloquine (0.42; 0.38-0.47; n = 26), and lumefantrine (0.31; 0.07-1.36; n = 9). Higher maternal body mass index was associated with a lower N/M ratio of desbutyl-lumefantrine. Female neonatal sex and a longer interval following drug administration were associated with higher N/M ratios of carboxy-mefloquine. No increased risk of jaundice was observed. Antimalarial drugs crossed the placenta variably. Neonatal concentrations ranged from less than half (lumefantrine, mefloquine) to near maternal equivalence (piperaquine). Collection of neonatal capillary samples at birth should be considered in future studies.SummaryWe compared antimalarial blood concentrations in mothers, neonates, and cords. Neonatal drug concentrations ranged from near maternal equivalence (piperaquine) to less than half (lumefantrine, mefloquine). Cord concentrations may underestimate neonatal exposure. Future studies should consider neonatal capillary sampling.